Following infection with Leishmania major (Lm), there is outgrowth of Th1 cells in mice that resolve the infection, but outgrowth of Th2 cell in mice that succumb to disease. This project will test 3 major subhypotheses: 1) To test the hypothesis that differential expression of MHC (I-A/E) and/or accessory (ICAM), LFA/co-stimulatory molecules (B7, CD40) by APCs and the secretion of monokines/factors by A{Cs influences Lm specific Th priming syngereic system; 2) to examine congenic/chimeric combinations of APCs and responding T cells to further test the hypothesis that APCs influence Th priming and to test additional hypothesis; 3) to monitor the expression of APC molecules important to T cell priming in cutaneous lesions of Lm and in the lymph nodes draining the lesion, and to test the hypothesis that factors that influence or are secreted by APCs (e.g., monokines, prostaglandin E2 (PGE2) affect Lm specific Th priming and the outcome of infection with Lm.